Top

Published in:

01-11-2012 | Laboratory Investigation

CDA-2 induces cell differentiation through suppressing Twist/SLUG signaling via miR-124 in glioma

Authors: You-ke Xie, Shao-fen Huo, Gong Zhang, Fu Zhang, Zu-ping Lian, Xiong-lin Tang, Chuan Jin

Published in: Journal of Neuro-Oncology | Issue 2/2012

Abstract

Cell differentiation agent-2 (CDA-2) is an extraction from healthy human urine consisting of primary organic acids and peptides, and it has been demonstrated to inhibit growth and induce differentiation in glioma and other cell lines. But the mechanism of CDA-2 remains unclear. In this study, we demonstrated that CDA-2 inhibited cell growth and induced differentiation of glioma cells, accompanied with decreased expression of SLUG, Twist and Vimentin in both SWO-38 and U251 cell lines. Overexpression of SLUG or Twist greatly eliminated the efficiency of CDA-2 in inducing differentiation. Further study showed that CDA-2 treatment resulted in great changed microRNAs (miRNAs) detected by quantitative PCR, in which miR-124 was one of the most changed miRNAs and its level was increased by fourfold. The result of miRNA target prediction showed that miR-124 could regulate hundreds of genes which were relative to cell differentiation, such as SLUG, Vimentin, actin cytoskeleton, focal adhesion, tight junction. Inhibition of miR-124 up-regulated SLUG, Twist and Vimentin proteins, and partly eliminated the function of CDA-2 on these mesenchymal markers. Our findings demonstrated for the first time that CDA-2 induced cell differentiation through suppressing Twist and SLUG via miR-124 in glioma cells.

Yao CJ, Lai GM, Chan CF, Yang YY, Liu FC, Chuang SE (2005) Differentiation of pheochromocytoma PC12 cells induced by human urine extract and the involvement of the extracellular signal-regulated kinase signaling pathway. J Altern Complement Med 11:903–908. doi:10.1089/acm.2005.11.903 PubMedCrossRef

Xin Y, Xu KS (2001) HPLC determination of peptide’s molecular weight in Niaoduosuantai (CDA-II) injection. Chin J Pharm Anal 21:191–193

Lu Z, Jia J, Di L, Song G, Yuan Y, Ma B, Yu J, Zhu Y, Wang X, Zhou X, Ren J (2011) DNA methyltransferase inhibitor CDA-2 synergizes with high-dose thiotepa and paclitaxel in killing breast cancer stem cells. Front Biosci 3:240–249. doi:10.2741/239

Wang HY, Zhong XY, Tu YS, Liu ZZ (2006) Effect of CDA-II on the differentiation and inhibition of human glioma cell lines SWO-38. Chin Pharm Bull 22:184–188

Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996. doi:10.1016/j.canrad.2005. 07.001

Lin CL, Wang MH, Qin YF, Fang M, Xie BB, Zhong XY (2009) Differentiation of SWO-38 glioma cells induced by CDA-2 is mediated by peroxisome proliferator-activated receptor γ. J Neurooncol 95:29–36. doi:10.1007/s11060-009-9900-x PubMedCrossRef

Huang J, Yang M, Liu H, Jin J (2008) Human urine extract CDA-2 induces apoptosis of myelodysplastic syndrome-derived MUTZ-1 cells through the PI3 K/Akt signaling pathway in a caspase-3-dependent manner. Acta Pharmacol Sin 29:951–964. doi:10.1111/j.1745-7254.2008 PubMedCrossRef

Peinado H, Cano A (2008) A hypoxic twist in metastasis. Nat Cell Biol 10:253–254. doi:10.1038/ncb0308-253 PubMedCrossRef

Elias MC, Tozer KR, Silber JR, Mikheeva S, Deng M, Morrison RS, Manning TC, Silbergeld DL, Glackin CA, Reh TA, Rostomily RC (2005) TWIST is expressed in human gliomas and promotes invasion. Neoplasia 7:824–837. http://www.ncbi.nlm.nih.gov/pubmed/16229805

10.

Ciafreà SA, Galardi S, Mangiola A, Ferracin M, Liu C-G, Sabatino G, Negrini M, Maira G, Croce CM, Farace MG (2005) Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun 334:1351–1358. doi:10.1016/j.bbrc.2005.07.030

11.

Wang T, Zhang L, Shi C, Sun H, Wang J, Li R, Zou Z, Ran X, Su Y (2012) TGF-β-induced miR-21 negatively regulates the antiproliferative activity but has no effect on EMT of TGF-β in HaCaT cells. Int J Biochem Cell Biol 44:366–376. doi:10.1016/j.biocel.2011.11.012

12.

Bullock MD, Sayan AE, Packham GK, Mirnezami AH (2012) MicroRNAs: critical regulators of epithelial to mesenchymal (EMT) and mesenchymal to epithelial transition (MET) in cancer progression. Biol Cell 104:3–12. doi:10.1111/boc.201100115 PubMedCrossRef

13.

Peng X, Guo W, Liu T, Wang X, Tu X, Xiong D, Chen S, Lai Y, Du H, Chen G, Liu G, Tang Y, Huang S, Zou X (2011) Identification of miRs-143 and -145 that is associated with bone metastasis of prostate cancer and involved in the regulation of EMT. PLoS ONE 6:e20341. doi:10.1371/journal.pone.0020341 PubMedCrossRef

14.

Andersen CL, Jensen JL, Orntoft TF (2004) Normalization of real-time quantitative reverse transcription-PCR data: a model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets. Cancer Res 64:5245–5250. doi:10.1158/0008-5472.CAN-04-0496 PubMedCrossRef

15.

Velpula KK, Dasari VR, Tsung AJ, Dinh DH, Rao JS (2011) Cord blood stem cells revert glioma stem cell EMT by down regulating transcriptional activation of Sox2 and Twist. Oncotarget 2:1028–1042PubMed

16.

Uziel T, Karginov FV, Xie S, Parker JS, Wang YD, Gajjar A, He L, Ellison D, Gilbertson RJ, Hannon G, Roussel MF (2009) The miR-17~92 cluster collaborates with the Sonic Hedgehog pathway in medulloblastoma. Proc Natl Acad Sci USA 106:2812–2817. doi:10.1073/pnas.0809579106 PubMedCrossRef

17.

Brabletz T (2012) MiR-34 and SNAIL: Another double-negative feedback loop controlling cellular plasticity/EMT governed by p53. Cell Cycle 11:215. doi:10.4161/cc.11.2.18900

18.

Yang G, Zhang R, Chen X, Mu Y, Ai J, Shi C, Liu Y, Shi C, Sun L, Rainov NG, Li H, Yang B, Zhao S (2011) MiR-106a inhibits glioma cell growth by targeting E2F1 independent of p53 status. J Mol Med (Berl) 89:1037–1050. doi:10.1007/s00109-011-0775-x

19.

Xia H, Cheung WK, Ng SS, Jiang X, Jiang S, Sze J, Leung GK, Gang L, Chan DT, Bian XW, Kung HF, Poon WS, Lin MC (2012) Loss of brain-enriched miR-124 enhances the stem-like traits and invasiveness of glioma cells. J Biol Chem 17:1–18. doi:10.1074/jbc. M111. 332627

20.

Casas E, Kim J, Bendesky A, Ohno–Machado L, Wolfe CJ, Yang J (2011) SLUG is an essential mediator of Twist-induced epithelial mesenchymal transition and metastasis. Cancer Res 71:245–254. doi:10.1158/0008-5472.CAN-10-2330 PubMedCrossRef

21.

Mikheeva SA, Mikheev AM, Petit A, Beyer R, Oxford RG, Khorasani L, Maxwell JP, Glackin CA, Wakimoto H, González–Herrero I, Sánchez–García I, Silber JR, Horner PJ, Rostomily RC (2010) TWIST1 promotes invasion through mesenchymal change in human glioblastoma. Mol Cancer 9:194. http://www.molecular-cancer.com/content/9/1/194

22.

Cheng L-C, Pastrana E, Tavazoie M, Doetsch F (2009) miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche. Nat Neurosci 12:399–408. doi:10.1038/nn.2294 PubMedCrossRef

23.

Yoo AS, Sun AX, Li L, Shcheglovitov A, Portmann T, Li Y, Lee-Messer C, Dolmetsch RE, Tsien RW, Crabtree GR (2011) MicroRNA-mediated conversion of human fibroblasts to neurons. Nature 476:228–231. doi:10.1038/nature10323 PubMedCrossRef

24.

Li KK, Pang JC, Ching AK, Wong CK, Kong X, Wang Y, Zhou L, Chen Z, Ng HK (2009) miR-124 is frequently down-regulated in medulloblastoma and is a negative regulator of SLC16A1. Hum Pathol 40:1234–1243. doi:10.1016/j.humpath.2009.02.003

25.

Pierson J, Hostager B, Fan R, Vibhakar R (2008) Regulation of cyclin dependent kinase 6 by microRNA 124 in medulloblastoma. J Neurooncol l90:1–7. doi:10.1007/s11060-008-9624-3

26.

Furuta M, Kozaki K, Tanaka S, Arii S, Imoto I, Inazawa J (2010) miR-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in hepato- cellular carcinoma. Carcinogenesis 31:766–776. doi:10.1093/carcin/bgp250 PubMedCrossRef

27.

Xia J, Wu Z, Yu C, He W, Zheng H, He Y, Jian W, Chen L, Zhang L, Li W (2012) miR-124 inhibits cell proliferation in gastric cancer through downregulation of SPHK1. J Pathol 227:470–480. doi:10.1002/path.4030

28.

Laine S, Alm J, Virtanen S, Aro H, Laitala–Leinonen T (2012) MicroRNAs miR-96, miR-124 and miR-199a regulate gene expression in human bone marrow-derived mesenchymal stem cells. J Cell Biochem 133:2687–2695. doi:10.1002/jcb.24144

29.

Zhou Y, Chen KS, Gao JB, Han R, Lu JJ, Peng T, Jia YJ (2012) miR-124-1 promotes neural differentiation of rat bone marrow mesenchymal stem cells. Zhong guo Dang Dai Er Ke Za Zhi 14: 215–220. http://www.cjcp.org/EN/Y2012/V14/I3/215

30.

Miranda KC, Huynh T, Tay Y, Ang YS, Tam WL, Thomson AM, Lim B, Rigoutsos I (2006) A pattern-based method for the identification of MicroRNA binding sites and their corresponding heteroduplexes. Cell 126:1203–1217. doi:10.1016/j.cell.2006.07.031 PubMedCrossRef

31.

Tay Y, Zhang J, Thomson AM, Lim B, Rigoutsos I (2008) MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation. Nature 455:1124–1128. doi:10.1038/nature07299 PubMedCrossRef

Title: CDA-2 induces cell differentiation through suppressing Twist/SLUG signaling via miR-124 in glioma
Authors: You-ke Xie
Shao-fen Huo
Gong Zhang
Fu Zhang
Zu-ping Lian
Xiong-lin Tang
Chuan Jin
Publication date: 01-11-2012
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 2/2012
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-012-0961-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

CDA-2 induces cell differentiation through suppressing Twist/SLUG signaling via miR-124 in glioma

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2012

miR-335 promotes cell proliferation by directly targeting Rb1 in meningiomas

Validation of the Mishel’s uncertainty in illness scale-brain tumor form (MUIS-BT)

Molecular genetics of adult grade II gliomas: towards a comprehensive tumor classification system

Declarative memory disorders in patients with brain tumors can improve after cognitive training intervention: evidence from functional MRI

Increased risk of cancer after Bell’s palsy: a 5-year follow-up study

Phase I trial of verubulin (MPC-6827) plus carboplatin in patients with relapsed glioblastoma multiforme